Staphylococcus aureus is a leading cause of serious hospital- and community-acquired infections. The discovery of serologically distinct capsular polysaccharides on the surface of clinical isolates has allowed the development of vaccines and passive protective immunity. We have studied patient characteristics, infection characteristics and the surface and capsular polysaccharide serotype distribution in patients with S. aureus infections complicated by bacteraemia admitted to VA hospitals in Maryland between 1995 and 2000. Nine hundred and ninety-three blood cultures from 331 patients were positive for S. aureus. Thirty-eight percent of patients had diabetes, 11% had end-stage renal failure, and 23% were injection drug users. Forty-two percent of infections were caused by methicillin-resistant strains (MRSA), and 60% were acquired during hospitalization. Serotyping of the first available isolate per patient (N=234 isolates) using polyclonal antibodies showed three major phenotypes--42%, type 8 (T8) capsule; 50%, type 5 (T5) capsule; and 8%, 336 polysaccharide. MRSA isolates were significantly more likely to be T5 than methicillin-susceptible isolates (66% vs. 39%, P<0.001). The proportion of T5 MRSA increased significantly (years 1-2: 41%; years 3-4: 65%; years 5-6: 90%, P<0.001). This large sample of patients with serious S. aureus infection confirms that capsular polysaccharides T5 and T8 cause most human infections, and together with serotype 336, account for nearly all those with bacteraemia.