Previous studies have shown the efficacy of parenteral immunization of volunteers with purified type 1 M protein against challenge with homologous streptococcui (J. clin, Invest. 52: 1885, 1973). A double-blind study was conducted on 21 adults immunized by aerosol-spray into the nasopharynx, and 23 controls who received saline placebo. Two booster doses were given at monthly intervals and approximately 30 days later vaccinees and controls were challenged with homologous streptococci (10-6/ml) by swabbing the pharyngeal-tonsillar areas. Throat cultures, leukocyte counts, temperatures and physical signs and symptoms were followed to assess infection. Illness was defined as a positive throat culture, oral temperature of larger than or equal to 38 degrees C, a WBC count of twice baseline or greater than 10,000 per mm-3, exudative pharyngitis and adenopathy. Of the 43 subjects, 13 were ill by all criteria (10 controls, 3 vaccinees [p smaller than .02]); 21 were well by all criteria (6 controls and 15 vaccinees); and 10 exhibited some but not all positive criteria (7 controls, 3 vaccinees). Positive throat cultures following challenge were obtained in 19 controls and 5 vaccinees (p smaller than 0.001). There was no correlation between the pre-challenge serum antibody titer and the development of subsequent illness. It is concluded that local topical immunization with a M protein vaccine offers significant type-specific protection against challenge with streptococci.