Morphine, an alkaloid known for its potent analgetic action, also affects a variety of immunologic functions. In the experiments reported here, the time course for the effect of 75-mg morphine pellet implants on spleen and thymus size and cellularity and in vitro proliferative responses of lymphocytes from male C3H/HeN mice is described. T lymphocyte proliferation in response to concanavalin A (Con A) was not significantly affected at 6 or 24 hr after morphine pellet implantation but was reduced at 48 and 72 hr. B lymphocyte proliferation in response to lipopolysaccharide was more sensitive to morphinization, as the response was reduced at the 24, 48 and 72 hr intervals after implantation of the morphine pellet. No differences in Con A- or lipopolysaccharide-induced proliferation were observed 96 hr after pellet implantation. Interestingly, a slight elevation of Con A-induced proliferation was observed 120 hr after morphine pellet implantation. By contrast with Con A proliferative data, lipopolysaccharide-induced proliferation of lymphocytes from morphine-treated mice was not different from placebo-pelleted mice at 120 hr. A marked atrophy of the spleen and thymus accompanied the reduced splenocyte proliferative responses of morphine-treated mice and was greatest at the 48 to 72 hr postimplantation interval. The attenuation of mitogen-induced proliferative responses and atrophy of immune organs was accompanied by hypothermia and a marked tolerance to the antinociceptive effect of morphine in morphine-pelleted mice at all of the time points that were monitored.(ABSTRACT TRUNCATED AT 250 WORDS)