&NA;We have previously described the isolation of a lipoidal splenic extract (LSE) that demonstrated a variety of hematologic effects including inhibition of platelet aggregation both in vivo and in vitro. Since endotoxin causes platelet aggregation and microembolism the protective effect of LSE in endotoxemia was examined in the present study. Both young and elderly Swiss mice given LSE 2‐3 hoursbeforeendotoxin challenge showed a statistically significant increase in survival compared with saline‐treated controls. However, no significant improvement in survival was noted when LSE was administeredat the same timeas endotoxin. These results add further support to the role of the spleen in the control of infection.