The overall fate of the quinolinemethanol antimalarial, mefloquine-HCl [WR 142,490, erythro-DL-alpha-(2-piperidyl)-2,9-bis(trifluoromethyl)-4-quinolinemethanol hydrochloride] was investigated in the rat with 14C-labeled drug. Despite its extensive binding to plasma proteins, high tissue/plasma concentration ratios were found. Fecal excretion accounted for most of the drug and metabolites. This fate was rationalized on the basis of physical properties of mefloquine (and its metabolites) and extensive biliary and gastric secretion, followed by reabsorption. Evidence was obtained for the formation of several metabolites. Limited studies were carried out in rats, dogs, and one human subject with another quinolinemethanol, WR 30,090-14C [DL-6,8-dichloro-2-(3',4'-dichlorophenyl)-alpha-(di-n-butylaminomethyl)-4-quinolinemethanol hydrochloride]. Its general fate and physical properties were similar to mefloquine. The disposition of the two quinoline compounds studied was compared to that of quinine and quinidine reported in the literature. This revealed that modification of the quinine molecule resulted in new drugs which were more highly bound and exhibited longer half-lives than quinine.