The behavioral effects of the histamine H1 antagonists d- and l-chlorpheniramine and of the H2 antagonist zolantidine were determined in squirrel monkeys responding under a fixed-interval (FI) 3-min schedule of stimulus-shock termination. Although d-chlorpheniramine is known to be much more potent than l-chlorpheniramine for antagonizing H1 receptor-mediated effects of histamine or displacing [3H]-mepyramine from histamine H1 receptors, similar doses of racemic chlorpheniramine and the d- and l-isomers (3.0-10.0 mg/kg) produced comparable increases in rates of responding. Zolantidine (1.0-17.0 mg/kg) did not alter or, at the highest dose, markedly decreased responding. These findings suggest that the psychomotor stimulant effects of chlorpheniramine involve actions other than the blockade of histamine H1 or H2 receptors. Selected H1 antagonists and cocaine are known to have comparable rate-increasing, reinforcing, and discriminative stimulus effects and, recently, the enantiomers of chlorpheniramine have been shown to displace [3H]-cocaine from binding sites in CNS with approximately equal potency. Possibly, such actions mediate behavioral effects common to H1 antagonists and cocaine.