This is a review of evidence for a circadian-mediated pharmacology of a single dose of hydrochlorothiazide in normal man. The normal circadian rhythms of urine volume and electrolytes are discussed in detail. Information is documented that hydrochlorothiazide diuresis, in normal subjects on a normal schedule of diurnal activity/nocturnal rest, progressively increases for 4 h after a.m. administration and for 8 h after p.m. administration. This suggests that the therapeutic efficiency of a single dose may be enhanced (nearly 50%) by the simple expedient of prescribing in the afternoon. No information is provided as to whether the circadian-mediated response appertains in disease or with continued drug administration. The word ‘circadian’ is not found in classical pharmacological texts although many examples of circadian-mediated drug action have now been described. A circadian reappraisal of drug effects in general is overdue.