Staphylococcal coagglutination was evaluated for detection of Streptococcus pneumoniae and Haemophilus influenzae antigens in vitro and in the clinical setting of acute pneumonia. Coagglutination testing was performed with Phadebact reagents and with polyvalent and type-specific reagents for pneumococci prepared in the laboratory. Purified capsular antigens of 10 of 14 pneumococcal serotypes (included in the current pneumococcal vaccine formulation) were detected by coagglutination in the range of 0.5-62 ng/ml; serotype 6 was detected at 125 ng/ml, and serotypes 12, 23, and 25 were detected only at 500 ng/ml or more. Haemophilus influenzae type b antigen was detected at 100 ng/ml. Sputum, blood, and urine specimens of 36 consecutive patients admitted with pneumonia were evaluated prospectively by coagglutination. Nonspecific reactions were eliminated by pretreatment with ethylenediaminetetra-acetic acid and heating and with staphylococcal protein A. Eight of nine patients with sputum cultures positive for pneumococci had positive sputum coagglutination (sensitivity of 89%); 24 of 27 patients with cultures negative for pneumococci had negative sputum coagglutination (specificity of 89%). Serum or urine coagglutination was positive in five patients with pneumococcal pneumonia, including the only bacteremic case, the only fatality, and another patient who had a protracted clinical course. In conclusion, coagglutination is a simple, rapid, sensitive, and specific test for antigen detection in patients with acute pneumonia.