The development of antibodies to teichoic acid was studied in 56 patients with infections due to Staphylococcus aureus. All 28 patients with endocarditis eventually developed teichoic acid antibodies demonstrable both by counterimmunoelectrophoresis and by gel diffusion; however, 7 patients were negative on admission. Eight of 15 patients with S. aureus bacteremia developed antibodies by counterimmunoelectrophoresis and 6 of the 8 were positive by gel diffusion; 4 of those 6 had evidence of seeding of S. aureus. Three of 5 patients with osteomyelitis and 1 of 8 with localized peripheral abscesses had teichoic acid antibodies. Titers of 1:4 or greater by gel diffusion were present in 18 of 28 patients with endocarditis compared with only 1 of 10 patients with nonendocarditic staphylococcal infections. Thus, the demonstration and quantitation of teichoic acid antibodies is of great clinical value in the early diagnosis of infections due to S. aureus and in assessing the likelihood of deep intra- or perivascular seeding.