In order to learn whether a complete exchange of dietary soy protein for casein causes a change of serum lipid levels in primates, 8 Macaca fascicularis monkeys were fed a semi-purified ration; its basic composition was similar to diets consumed in Western Europe. In a crossover experiment, casein was exchanged for a soy protein isolate and vice versa. Plasma and lipoprotein cholesterol and triglyceride levels were determined following a 3-week dietary regimen. There was no significant difference of total serum cholesterol levels between the soy protein and casein periods (4.6 vs. 4.7 mmol/l). However, high-density lipoprotein (HDL) cholesterol levels were significantly higher (1.6 vs. 1.2 mmol/l, p < 0.01) and very-low-density lipoprotein (VLDL) cholesterol levels were significantly lower (0.39 vs. 0.55 mmol/l, p < 0.01) following the soy protein diet. There was no distinct change in total or lipoprotein triglyceride levels following exchange of the dietary protein. It is concluded that in nonhuman primates a complete exchange of soy protein for casein produces changes of HDL, but not of total or low-density lipoprotein (LDL) cholesterol.