Isoprinosine is a compound developed for antiviral use. The effects of isoprinosine on mouse responses to sheep red blood cells were studied over a wide range of doses, from 0.5 microgram/kg to 5 g/kg, i.p. administered at the time of i.v. immunization or as pretreatment for 7 days before antigenic stimulus. Low doses, 50 microgram/kg to 50 mg/kg, significantly increased the numbers of IgM- or IgG-spleen antibody-forming cells. Large doses, such as the LD50 (5 g/kg) or pretreatments where unable to impair mouse immune responsiveness. Isoprinosine (< 500 mg/kg/day) orally administered at time of or one day after immunization stimulated immune responses. In vitro addition of isoprinosine to spleen lymphocytes augmented PHA- or Con A-induced proliferation over a concentration range from 10 to 150 microgram/ml, whereas isoprinosine had no effect in the absence of mitogens. These data, and the lack of immunodepressing effect, suggest that there is a need for further evaluation of isoprinosine as an immunopotentiator.