Abstract Initial acute behavioral studies in mice indicated that phencyclidine (PCP) produced marked motor impairment as measured by the inverted screen technique with an ED 50 value of 4.1 μMole/kg (i.v.). Phenylcyclohexene (PC) was considerably less active with an ED 50 value of 325 μMole/kg (i.v.). PCP was also shown to be more lethal than PC as acute (24 hr; i.v. injection) LD 50 values (μMoles/kg) in males were 57 and 448, and in females were /6 and 425, respectively. A greater acute lethality was also produced by PCP after i.p. and p.o. administration. Subchronic (14-day) exposure (i.p.) to PCP at doses up to ≈40 percent of the acute LD 50 value (123.6 μMole/kg, i.p., daily) was without significant effect on body and organ weights, hematology and clinical chemistry, and humoral and cell-mediated immunity. Higher doses of PCP were not possible because of acute lethality. Subchronic exposure to PC (63.4, 317, and 634.5 μMoles/kg; 4 percent, 20 percent and 40 percent of acute i.p. LD 50 value, respectively) produced several marked effects. At the highest dose tested, body weight and thymus weight in both males and females, and liver weight in males were significantly decreased. The spleen weight of males exposed to 317 μMole/kg PC was also significantly decreased. Humoral immunity (production of antibody forming cells) was significantly inhibited in both males and females exposed to PC. In contrast, cell-mediated immunity (development of a delayed-type hypersensitivity response) was only significantly inhibited in females. As PCP has no measurable toxicity under these conditions and PC produced significant effects at relatively high doses, the results suggest that neither chemical is exceptionally toxic following subchronic exposure.