Thrombocytopenia is a dose-limiting toxicity of macrophage colony- stimulating factor (M-CSF) in preclinical and initial phase I trials. Modulation of macrophage-mediated platelet destruction in immune thrombocytopenic purpura (ITP) may be affected by M-CSF activity. In this study, plasma levels of M-CSF were determined by a sensitive radioimmunoassay in 23 patients with ITP. These were compared with control levels measured in 24 healthy subjects. M-CSF levels were significantly higher in the ITP patients than in the control subjects (218 v 179, P < .02); however, there was a great deal of overlap. The highest M-CSF levels (median = 299 U/mL) were observed in three patients with Evan's syndrome. Patients with severe ITP (platelets < 25,000/microL) had intermediate M-CSF levels (median = 231 U/mL) and those with mild thrombocytopenia (> 25,000/microL) had normal levels (median = 173 U/mL). Sixteen patients were treated with corticosteroids: 10 responded and 6 did not. Median M-CSF levels were higher in those who failed to respond compared with responders (272 v 202, P < .05). These findings suggest M-CSF may influence macrophage- mediated platelet destruction in ITP.