Interleukin (IL)-13 is a newly described cytokine expressed by activated lymphocytes. We examined the effects of the murine recombinant cytokine on the phenotype and activation status of elicited peritoneal macrophages (M phi), concentrating on activities which are known to be modulated by interferon-gamma and IL-4. IL-13 markedly suppressed nitric oxide release and to a lesser extent secretion of the pro-inflammatory cytokine tumor necrosis factor-alpha. However, antimicrobial capacity was not completely jeopardized as the respiratory burst was unaffected, and indeed the enhanced expression of M phi mannose receptor and major histocompatibility class II, and regulation of sialoadhesin, the M phi sialic acid-specific receptor involved in hemopoietic and lymphoid interactions, suggest that these cells are not simply deactivated, but primed for an active role in immune and inflammatory responses. These activities closely mimic those of IL-4, but mediation of the effects by IL-4 was discounted by the use of a neutralizing monoclonal antibody. Thus, IL-13, like IL-4, is a cytokine which has complex effects on M phi behavior, inducing activities characteristic of both activation and deactivation.