The antinociceptive effect of (+/-)-3-alpha-tropanyl 2-(4-Cl-phenoxy)butyrate [corrected] (SM-21) (10-40 mg kg(-1) s.c., 10-30 mg kg(-1) i.p., 20-60 mg kg(-1) p.o., 3-20 mg kg(-1) i.v. and 5-20 microg per mouse i.c.v.) was examined in rodents and guinea pigs by using the hot-plate, abdominal constriction, tail-flick and paw-pressure tests. The antinociception produced by (+/-)-SM-21 was prevented by atropine, pirenzepine and hemicholinium-3 but not by quinpirole, R-(alpha)-methylhistamine, [1-[2(methylsufonyl)amino]ethyl]-4-piperidinyl]methyl-5-floro++ +-2-methoxy-1H-indole-3-carboxylate hydrochloride, N6-cyclopentyladenosine, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide, naloxone, 3-aminopropyl-diethoxy-methyl-phosphinic acid or reserpine. On the basis of the above data, it can be postulated that (+/-)-SM-21 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. Affinity profiles of (+/-)-SM-21 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4) have shown a selectivity ratio M2/M1 of 4.6 that, although very low, might be responsible for the antinociception induced by (+/-)-SM-21 through an increase in ACh extracellular levels. In the antinociceptive dose range, (+/-)-SM-21 did not impair mouse performance evaluated by the rota-rod and hole-board tests.