Although rat peritoneal neutrophils in the presence of cytochalasin B demonstrate superoxide (O2-) responses to the chemotactic peptide N'-formyl-met-leu-phe (FMLP), neither elicited rat peritoneal macrophages nor rat alveolar macrophages show an O2- response to FMLP (in the presence or absence of cytochalasin B), although a good O2- response to opsonized zymosan is demonstrated by both types of macrophages. Using Fura-2 loaded cells, peritoneal macrophages failed to show an increase in intracellular calcium after exposure to FMLP, f-nor-leu-phe, F-met-met-met, or F-norleu-leu-phe-norleu-lys. FMLP also failed to induce elevations in intracellular calcium in alveolar macrophages. In 3H-FMLP binding studies, the lack of responsiveness of peritoneal and alveolar macrophages was associated with the lack of FMLP receptors on these cell types, in striking contrast to the presence of functional receptors on rat neutrophils.