I. The effects have been compared of long-term administration of similar amounts of ethanol given either diluted in drinking water or spaced out in the form of intoxicating doses.2. The effect of ethanol on the development of liver lesions produced by a marginal diet was examined. The measurements of growth rate, water balance, plasma glucose and electrolytes, rate of ethanol elimination, and some behavioural tests for the detection of tolerance and possible signs of neurological disturbance were also included.3. Isocalorically pair-fed growing male rzts were subjected to three different regimens for 6 months: (A) ethanol solution as the sole drinking fluid with z days' intake adjusted to approximately j mg/g body-weight ; ( 8 ) a similar quantity of ethanol given as a single intoxicating dose per 0s on alternate days; (C) oleic acid isocaloric with the ethanol per 0s on alternate days. 4. All the regimens caused fatty liver. Hepatic fibrosis, as judged macro-and microscopically, was equally severe after treatments A and C , but milder after treatment B.j. Growth was retarded by intoxication, which also brought about a large increase in water consumption, without exerting other clear effects on water balance or on plasma electrolytes.The rate of ethanol elimination was increased by repeated intoxication. Behavioural tolerance of the effects of ethanol was also found in the animals subjected to intoxication.Nutritional and pharmacological factors both produce effects on the organism after long use of alcoholic beverages. The amount of ethanol consumed determines its role in the nutritional balance, whereas the temporal distribution of the intake is decisive for the intensity of the pharmacological effects. Improvement in the differentiation between these two aspects of the action of ethanol would serve to advance our understanding of how the hazards involved in the use of alcoholic beverages could be mitigated. Notwithstanding the importance of these considerations, little systematic exploration of the respective roles of the pharmacological and the nutritional effects of ethanol has been made. In long-term experiments with animals, the most common technique has been to provide ethanol solution as the sole source of fluid. Reports have been published also on various effects of intoxicating doses repeated over prolonged periods. There does not seem, however, to be any report of studies in which other conditions have been kept constant, and only the method of administration of a given quantity of ethanol has been varied. The purpose of the present study was to examine this approach, and find criteria for further investigations along similar lines. A further aim was to simulate conditions of a regular but relatively moderate drinking pattern, rather than heavy drinking. A brief preliminary report has been published (Wallgren & Suomalainen, 1966 E X P E R I M E N T A L Criteria of ethanol effectsAs the study was exploratory, broad criteria were chosen. Fatty infiltration and fibrosis of the liver objectively show ef...

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