It is well known that splenectomy causes immunologic impairment and increases susceptibility to infection; however, the time course of reticuloendothelial depression and of alterations in hepatic and pulmonary retention of injected lipid emulsion following splenectomy is not known. To determine this, rats were splenectomized and reticuloendothelial function evaluated at various intervals following splenectomy by measuring the intravascular clearance of131I-triolein gelatinized lipid emulsion. The intravascular clearance (T/2) and lung uptake of the lipid emulsion increased and hepatic uptake of emulsion decreased 4 to 8 hours following splenectomy. One day following splenectomy, although the T/2 appeared normal, the lung uptake was 1,123% higher and hepatic uptake was still 33% lower than control. The T/2 and hepatic retention returned to normal 2 days following splenectomy; however, the lung retention was higher than controls even 10 days following splenectomy. In another set of experiments, splenectomy was performed following which sepsis in rats was produced by cecal ligation and puncture. Ten hours following cecal ligation and puncture, the gangrenous cecum was removed and survival was measured over 5 days. The mortality rate in these animals was 57% (12/21) compared to 0% (0/8) in nonsplenectomized cecal ligated and punctured animals. These results suggest that splenectomy may not only have deleterious effects in terms of the host defense system, but may also cause prolonged pulmonary changes.