Protective effects of continuous administration of physostigmine alone, or in addition to scopolamine, against soman-induced toxicity were studied in guinea pigs. The results clearly demonstrated that treatment with physostigmine continuously via implanted mini-osmotic pumps for 4 or 7 days prior to soman exposure significantly protected from soman-induced mortality. In vehicle-infused guinea pigs, tremors, convulsions and loss of righting reflex occurred prior to their deaths induced by soman. Although all of the guinea pigs which received physostigmine pretreatment for 4 days prior to soman administration also displayed soman-induced tremors and convulsions, the onsets of these symptoms were significantly delayed. When animals continuously treated with physostigmine received injections of scopolamine 10 min prior to soman injections, there was a decreased incidence of all three toxicity symptoms as well as an increase in the latency to onset of tremors. Scopolamine was also able to reverse toxicity symptoms when soman was administered earlier. In animals which had been continuously treated with physostigmine via mini-osmotic pumps, the protective action against soman-induced toxicity was still apparent. On the contrary, acute physostigmine administration failed to protect against soman lethality. The present results suggest that the prophylactic uses of physostigmine via mini-osmotic pumps might be more useful than the acute bolus administration of physostigmine.