Intraperitoneal administration of lauric acid (C12) at the high doses, 100-1000 mumol/kg, showed weak but dose-dependent antinociceptive effect in mice. Pretreatment of the animals with 0.1 mumol/kg of i.p. C12 tended to suppress the antinociceptive effect of 7 mg/kg of s.c. morphine and daily combination of this dose of C12 with 10 mg/kg of s.c. morphine blocked the development of antinociceptive tolerance to morphine. However, increasing or decreasing of the dose of C12 resulted in the loss of its modulatory effect on morphine. The strict dose-dependency of C12 in its action on morphine suggests that there is a regulatory role for C12, a medium length straight chain fatty acid, in the endogenous pain inhibitory system.