Lymphoid cells from the C3H/HeJ mouse respond abnormally to bacterial lipopolysaccharide (LPS) in a number of in vitro functions. Abnormalities in both macrophage and lymphocyte populations have been suggested. In the present study, splenic mononuclear cells were isolated from C3H/HeJ, C3H/St, A/J, and BALB/c mice, and analyzed for mitogenesis and induction of procoagulant activity (PCA) by LPS prepared by either phenol or butanol extraction methods. All strains responded vigorously with resultant increased 3H thymidine uptake to Con A and PHA, and all but the C3H/HeJ responded well to butanol or phenol extracted LPS. However, the C3H/HeJ was unresponsive to phenol-extracted LPS and exhibited a poor but significant response to butanol-extracted LPS. In contrast, lymphoid cells from all strains, including the C3H/HeJ, exhibited a marked and equal increase of PCA in response to both phenol- and butanol-extracted LPS by using both splenic and peripheral blood lymphoid cells. The results obtained indicate that although the C3H/HeJ mouse may be unresponsive to a number of LPS-stimulated functions, there is no associated defect in PCA generation, a lymphocyte collaboration-dependent event.