Chemical pretreatment is effective against a 2 LD50 challenge of soman, sarin or VX or a 5 LD50 challenge of tabun. Chemical pretreatment followed by post challenge therapy should be effective against greater levels of agent. Such tests in guinea pigs are reported here; pretreatment regimens (PRGs) consisted of physostigmine (0.15 mg/kg, im) and an adjunct. The adjuncts [mg/kg, im] used were aprophen [8], atropine (AT)[16], azaprophen (AZA)[5], benactyzine [1.25], benztropine (BT) [4], scopolamine [0.08] and trihexyphenidyl [2]. Pretreatment was given 30 min before, and atropine (16 mg/kg, im) and 2-PAM (25 mg/kg, im) therapy (T) at one min after, 5 LD50s of agent. Results indicate that, all of the PRG+T regimens, except BT-not tested with T, prevent lethality by soman; trihexyphenidyl and scopolamine (the only adjuncts used therein) regimens each prevent lethality by sarin and VX. Against soman, all PRG+T regimens (vs PRG only) may shorten the median recovery time to 2 hrs or less. Even without therapy, the PRGs containing AT, AZA or BT prevent lethality by 5 LD50s of soman; however, used alone, only the PRG containing AZA reduces the incidence of convulsions at this level of soman.