The alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) enhanced the levels of plasminogen activator (PA) activity in fibroblast cells derived from the skin of patients with tuberous sclerosis. The enhanced enzyme levels were not correlated with those of cloning efficiency nor those of DNA synthesis after MNNG treatment. Enzyme enhancement was also observed in fibroblasts of ataxia telangiectasia and in human neoplastic glia cells, but not in fibroblasts of normal children. The PA induction test may be sufficiently sensitive for the detection of the cellular defects of tuberous sclerosis.