Pneumococcal vaccination following splenectomy is widely used as prophylaxis against overwhelming postsplenectomy infection. There remains controversy however, over the timing of vaccination. We hypothesized that delaying vaccination would increase the antibody response. Pneumococcal vaccinations were given at designated intervals to rats that had undergone either a sham abdominal surgery or splenectomy. Sixty male Sprague-Dawley rats, 250 to 400 g, were divided into three groups for vaccination: I, 1 day postoperatively; II, 7 days postoperatively; and III, 28 days postsplenectomy/sham. Serum antibody levels were then determined by enzyme-linked immunosorbent assay at 5 and 21 days after vaccination. Immunoglobulin (Ig) levels after delayed vaccination at 1 week postoperatively and 1 month postoperatively were significantly higher than levels from rats vaccinated 1 day postoperatively. IgM levels after vaccinations 1 week and 1 month postoperatively were also significantly higher than levels of rats vaccinated 1 day postoperatively (P < 0.05 for both IgG and IgM). On the basis of these results, we conclude that delaying vaccination after splenectomy enhances antibody responses.