Studies were done in selected groups of nonhuman primates in which the diet (low fat and high fat as either polyunsaturated or saturated fat), gender, and species (African green monkeys and cynomolgus monkeys) were varied. Large differences In plasma lipld and llpoprotein concentrations were found among these groups, providing the opportunity to examine their relationships to postheparin lipolytic activities (PHLA) including lipoproteln llpase (LPL) and hepatic trlglycerlde lipase (HTGL). PHLA was measured in plasma drawn 20 minutes after injection of heparin (100 units/kg). The assay was done with a radioactive trlglyceride emulsion, and LPL and HTGL activities were estimated after 1 M NaCI Inhibition of the former. LPL activity was high in both species of monkeys, and HTGL activity was low; the ratio of HTGL/LPL was consistently less than 0.5. The mean values for LPL activity did not vary significantly among experimental groups, but significant negative correlations between LPL activity and plasma trlglycerlde concentration were found. Statistically significant diet, species, and gender differences In HTGL activities were found. In hlgh-fat-fed compared to low-fat-fed animals, HTGL activities were higher, and high density llpoprotein (HDL) cholesterol concentrations and the percentages of HDLa, were also higher. African green monkeys had consistently higher HTGL activities than cynomolgus monkeys and had higher concentrations of HDL cholesterol and a greater proportion of HDL as the larger HDL 2b subtraction. Significantly lower HTGL activities were found in females compared to males fed the low-fat diets, and females had a significantly greater proportion of total HDL in the HDL 2b subtraction. In conclusion, these studies have shown that postheparin lipolytic activity in nonhuman primates Is responsive to species, diet, and gender differences and that this response is primarily in HTGL In most cases, total HDL cholesterol concentration and the proportion of HDL as the HDLa, subtraction were higher In groups with higher HTGL activity. If plasma HDL concentration and subtraction distribution are affected by HTGL to decrease HDL and the amounts of larger HDU subtractions, as has been often suggested by others, then our data show that other factors can override this relationship. LPL activity was consistently twofold greater than HTGL activity among the various groups, a finding that may partially explain the low plasma triglycerlde concentrations common in nonhuman primates.