Lymphocytes isolated from two inbred mouse strains that differed in their genetically determined sensitivity to heat-induced exencephaly were used to compare the in vitro kinetics of heat shock protein synthesis in the two strains following hyperthermic exposure. Differences in protein synthesis were determined by densitometric analysis of autoradiograms of SDS-PAGE gels. The findings were consistent with those observed in vivo in that there was an immediate and prolonged synthesis of heat-shock proteins by lymphocytes from the heat sensitive SWV/SD strain, compared to the response observed in lymphocytes from the heat-resistant DBA/2J strain. These results indicate that an in vitro lymphocyte assay of the heat-shock response may be a useful tool for screening suspected teratogenic agents.