We have investigated the effect of adenovirus 2 (Ad2) infection on human monocytes and monocyte-derived macrophages with regard to expression of TNF-alpha and IL-1 beta. In monocytes, the virus was bound to the surface without being internalized. On the other hand, Ad2 was internalized by macrophages. No virus replication and no transcription of the Ad2 early genes was observed in either of the cells. Ad2 infection induced transient increase in the mRNA levels for TNF-alpha and IL-1 beta in both monocytes and in macrophages, although the kinetics of the transcription was slightly different. The production of both cytokines, measured by ELISA tests, was enhanced in monocytes. In macrophages, a slight enhancement of TNF-alpha production was seen, whereas IL-1 beta was not detected. The data indicate that cellular genes might be activated by Ad2 virus infection in nonpermissive cells where no viral gene products could be detected.