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Abstract: Patients treated with monoclonal antibodies and cytokines for cancer receive often co-medication, which may influence treatment efficacy. Therefore, we investigated with a flowcytometric cytotoxicity assay the effect of several immunomodulatory drugs on antibody dependent cellular cytotoxicity (ADCC), interleukin-2 (IL-2) induced cytotoxicity and IL-2-induced-ADCC. We found that dexamethasone markedly inhibited the IL-2 induced cytotoxicity and the IL-2-induced-ADCC. Ondansetron, a 5-HT-3 serotonin receptor antagonist augmented significantly ADCC. Clemastine, a histamine type-2 receptor antagonist augmented the IL-2-induced-ADCC. The TNF antagonist thalidomide suppressed ADCC whereas pentoxifylline proved to be ineffective. Other tested drugs namely ibuprofen and indomethacin, both prostaglandin E2 antagonists, cimetidine a histamine type-2 receptor antagonist, the opioid pethidine, prostaglandin E2 and histamine exerted minor effects or had no influence on the tested parameters. We conclude that glucocorticosteroids should be avoided with monoclonal antibody and cytokine treatment. According to our in vitro data the other drugs tested did not have a negative impact on cellular cytotoxicity and ADCC. [Copyright &y& Elsevier]