Sequential skin responses to dinitrochlorobenzene challenge and repeat assays of serum antibody titer after two injections of bovine serum albumin were used as functional indices of cellular and humoral immunocompetence following hyperthermia in normal adult New Zealand White rabbits. The animals were subjected to different degrees of local hyperthermia by watercuff or radio-frequency heating of the normal thigh muscles maintained at 42 degrees for 1 hr on 3 consecutive days or 47--50 degrees for 30 min, respectively, or to total body hyperthermia (42 degrees for 1 hr on three occasions) in a humidified incubator. No alteration occurred in the response of heated rabbits to dinitrochlorobenzene challenge over a 3-month period. The humoral immune response to bovine serum albumin was significantly depressed (p less than 0.02) in the treated animals, and the reduction was independent of method and degree of heating. The results suggest that the B-lymphocytes are more susceptible to hyperthermic damage than is the T-cell population.