The IgG antibody responses to pneumococcal surface protein A (PspA) and capsular polysaccharides in acute and convalescent phase sera from 10 adult patients with invasive pneumococcal disease were analysed. The relatedness between the strains were characterised by capsular serotyping (1, 4, 7F, 9V, 12F and 19F), multi-locus sequence typing (MLST) and sequencing of the gene coding for PspA. Immunoblotting with the patient's own infecting strain used as whole cell antigen revealed strong antibody responses to PspA in 4 out of 10 patients. Two of these patients showed cross reactivity of PspA antibodies within PspA families 1 and 2 by ELISA measurements with recombinant PspA proteins. Using ELISA we found increased levels of capsular specific antibodies during convalescent phase in 9 out of 10 patients. All patients, except one, revealed low antibody levels in their acute phase sera. The binding of serum antibodies to live pneumococci using the patient's own infective strain was measured by flow cytometry. The antibodies binding to the live pneumococci corresponded to the serotype-specific polysaccharides by ELISA. Low antibody binding activities to their infective strain in the acute serum, may explain why they were not protected.