In vitro or in vivo infection of canine mononuclear cells by canine distemper virus (CDV) in short-term microcultures resulted in suppression of lectin-induced 3H-thymidine incorporation. This suppressive effect was also evident in pokeweed mitogen-driven in vitro immunoglobulin synthesis and release. Lectin-induced interleukin-2 production by monocyte-depleted lymphocyte cultures was marginally affected by CDV, whereas interleukin-1 production by adherent mononuclear cells was significantly depressed. Monocyte cultures established from viremic dogs released prostaglandin (PG)E2. The results suggest that, in addition to a direct viral effect upon lectin responsive cellular population(s), CDV modulates monocyte functions by inhibition of interleukin-1 production and by enhancing PGE2 release.