Repeat (booster) pneumococcal vaccination was administered to 32 patients with sickle cell disease in a double blind, placebo-controlled crossover study as early as 2.3 years after initial immunization. A significantly greater proportion of patients reported local pain, swelling or redness after booster, as compared to that after placebo (P less than 0.001), and pneumococcal antibody titer before vaccination was the predominant predictive variable for the development of fever, local pain and swelling after booster. A comparison of reaction rates following primary or booster immunization showed no significant differences in the frequency of reported symptoms except for muscle pain which occurred less frequently after booster (P less than 0.005). The concern for adverse reactions after repeat pneumococcal vaccination should not be an obstacle to the pursuit of further studies on the efficacy of pneumococcal vaccine and booster responses.