Procoagulant activity (PCA) of peripheral blood mononuclear cells was studied in vitro in 14 consecutive patients with essential mixed cryoglobulinemia (EMC). Mononuclear cells tested immediately after isolation expressed significantly higher PCA than cells from a matched control group (P less than 0.01). PCA generated by patients' cells after incubation at 37 degrees C for four hours without any stimulant was significantly higher than that produced by control cells (P less than 0.001). Lower mononuclear cell PCA was observed in the subgroup of patients treated with low doses of prednisone than in untreated patients. In two patients given high-dosage prednisone, cell PCA was markedly reduced. These findings suggest that mononuclear cells may be activated for PCA production in vivo by cryoglobulins or other unknown stimuli. Mononuclear phagocytes, by producing PCA in vivo, might be directly implicated in the local fibrin deposition in tissue lesions of EMC.