Treatment in vitro of Ehrlich ascites tumor cells or human fibroblasts with 8-methoxypsoralen (8-MOP, 2.4 microM) and UVA irradiation results in a 30% and 60% respectively reduction in lysosomal beta-galactosidase activity in situ. Under identical conditions one 8-MOP adduct was formed per 2 X 10(4) bases of DNA, one 8-MOP adduct was formed per approximately 10(4) tRNA molecules and one per approximately 100 ribosomes. It is suggested that the decrease in lysosomal beta-galactosidase activity is a result of leakage through the lysosomal membrane caused by psoralen-UVA damage of the lipids in the membrane, since no effect was found on beta-galactosidase in vitro. These results indicate that the lysosomes may also be a target for cellular photodamage by 8-methoxy-psoralen.