Cross‐protection of channel catfish (Ictalurus punctatus Rafinesque) immunized with a low dose of virulent Edwardsiella ictaluri and challenged with six E. ictaluri strains was examined in four trials. The relative per cent survival among low‐dose immunized and then challenged fish ranged from 27.7% to 100%. Significant protection (P<0.05), with the exception of strain ATCC‐33202, was conferred by immunization with a given E. ictaluri strain challenged either with a homologous or a heterologous strain. Antibody titres of pooled serum collected on day 22 from surviving fish examined by enzyme‐linked immunosorbent assay (ELISA) ranged from 1:40 to 1:320, but no differences were apparent among different vaccinated groups. The protein profiles of six E. ictaluri strains examined by Sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) showed a relatively homogeneous pattern. Immuno‐blots probed with pooled serum from immunized and challenged fish showed a pattern similar to LPS‐reaction patterns observed with E. ictaluri in other studies. Since the present studies further corroborate that E. ictaluri is a clonal bacterial species with no apparent antigenic differences, it is possible that immunization with a single E. ictaluri field strain should confer protection against any other strain.