Interferon (IF), one of the most controversial drugs in cancer therapy, induces a variety of CNS side effects. Therefore, IF was tested on single neuronal activity and compared with other drugs. Recombinant leukocyte A IF, morphine sulfate and L-glutamate were applied microiontophoretically to 18 cortical and 29 thalamic neurons. The majority of the cortical cells were excitated by IF while most of the thalamic cells did not respond to IF; however, morphine and glutamate elicited on these neurons the expected effects. IF produced a long-lasting increase in firing discharges and exhibited dose-response characteristics.