The possible presence of a toxic substance in the serum of patients with Kawasaki disease (KD) causing the pathogenesis of the disease was investigated by examining the effects of acute phase serum (Kawasaki serum, KS) from 9 patients with KD on viability and growth of cultured calf aortic smooth muscle (SMC) and endothelial cells (EC). All sera were heat inactivated, and filter sterilized. DNA content of these cultures incubated with KS (5%) and in age-matched control sera (CS) were similar after 3 d. (10.4 ± 0.4 vs. 11.8 ± 0.6 ug/cm for EC; 3.0 ± 0.3 vs. 2.4 ± 0.3 ug/cm for SMC). In these cultures, the rates of protein synthesis measured by tyrosine incorporation from 72-96 h was 7.8 ± 0.5 vs. 8.2 ± 0.5 nmol tyr/24 h/cm in EC, and 3.0 ± 0.4 vs. 2.2 ± 0.2 nM tyr/cm /24 h in SMC (N.S.). In independent experiments, KS (10%) promoted DNA and protein synthesis by SMC and EC over 24 h to the same extent as CS (10%). No cytopathic effect due to KS was observed by phase contrast microscopy at any time point or concentration (from 2-10%). Using DNA content, rates of protein synthesis, and morphologic criteria of viability we observed no difference between the effects of KS and CS on SMC and EC. Therefore, a direct toxic effect of KS does not appear to explain the pathogenesis of the arterial lesions that characterize Kawasaki disease.