A rat model was used to evaluate the possible effect on experimental postsplenectomy sepsis of a human gamma-globulin preparation for intravenous use (Sandoglobulin). Sixty splenectomized male Sprague-Dawley rats were given 3 X 10(3) Streptococcus pneumoniae type 1 intravenously. Twelve of the animals received no treatment and all died, in contrast to 12 sham-operated controls which all survived the challenge. The remaining splenectomized rats were divided into four groups, each consisting of 12 animals. One group was given 120 mg human gamma-globulin twice intraperitoneally (0.3 g/kg body wt), at 18 and 42 hr, after challenge; 10 of the 12 survived, in contrast to none of the 12 in the second group receiving 120 mg human albumin instead of gamma-globulin (P = 0.00003). When the injections were delayed to 24 and 48 hr, 9/12 gamma-globulin-treated animals still survived, in contrast to 0/12 in the albumin group. These findings point to new possibilities for treatment and perhaps prevention of overwhelming postsplenectomy sepsis by administration of high doses of gamma-globulins.