The relationship between respiratory syncytial virus (RSV) strain and disease severity was assessed in 265 hospitalized infants over a 3-year period (1988-1991). A severity index of clinical and physiologic parameters was used to grade illness severity. Multivariate analysis of 134 infants infected with group A RSV strains and 131 infants infected with group B strains indicated that prematurity, underlying medical conditions, group A RSV infection, and age < or =3 months were independently associated with severe disease. Odds ratios for severe disease for these risk factors were 1.83, 2.84, 3.26, and 4.39, respectively. Among infants without underlying medical conditions, group B RSV infection rarely required ventilatory support, in contrast to group A infections (1/90 vs. 13/107; P < .006), and had significantly lower severity indices (mean +/- SD, 0.6 +/- 9 vs. 1.3 +/- 1.9; P = .05). Results confirm earlier findings that group A RSV infection results in greater disease severity than group B infection among hospitalized infants.