We report here that tumor necrosis factor alpha (TNF) induces peculiar cytoplasmic vesicles in the human erythromyeloid leukemia cell line K 562, sensitized to the cytotoxic action of TNF by a treatment with the inhibitor of transcription actinomycin D. These vesicles are well delineated ultrastructurally. The formation of these vesicles is characteristic for the combination of actinomycin D with TNF and precedes the changes of apoptosis and cellular disintegration. These vesicles correspond to an intermediate step in the cytotoxicity caused by TNF and may indicate that reactive metabolites are involved in the mechanism of action of TNF.