The notion that the S1 subunit of the spike glycoprotein (S) of infectious bronchitis virus (IBV) is the major inducer of protective immunity has been examined. Groups of 10 1-day-old chicks were vaccinated with isolate UK/6/82 and challenged in-tranasally 3 or 6 weeks later with strains whose S1 protein differed from that of UK/6/82 to different extents: NL/D207/79, UK/142/86 and UK/167/84 (2%), UK/123/82 (4%), UK/918/67 (19%), USA/M41/41 and Portugal/322/82 (20%; both of the Massachusetts serotype), and NL/D1466/79 (49%). Four days after challenge tracheas were removed and observed for ciliary activity. Overall, the degree of cross-protection induced by UK/6/82 diminished as the similarity of the S1 proteins diminished, although in only two cases was the protection induced statistically less (P< 0.10) against the heterologous isolates than against the homologous strain. Even when a group as a whole was poorly protected against heterologous challenge, some individual chicks, including some challenged with D1466, exhibited high protection of the trachea. Conversely, in groups where protection was high overall, a few individuals were poorly protected. The results broadly support the view that differences in the sequence of the S1 protein do contribute to the ability of an IBV strain to break through the immunity induced by another strain. However, they also indicate that some conserved sequences in S1 and/or epitopes in the other, less variable, proteins also contribute to immunity. Moreover, individual chicks can differ greatly in their response to vaccination with IBV, a factor which should not be overlooked.