Entamoeba histolytica is susceptible to complement attack in its lumen-dwelling state and develops complement resistance during pathogenic tissue invasion. As experimental evidence suggests that this change in phenotype is accompanied by a change in gene expression, we constructed a subtractive cDNA library to identify genes involved. Poly(A) + RNA from complement-sensitive trophozoites was subtracted from single stranded cDNA derived from complement-resistant ones. Transcripts enriched in the library were found to code for a putative polypeptide comprising all sequence elements characteristic for serine/threonine protein kinases. The gene contains an intron of 46 nucleotides and two polyadenylation sites. Northern-blot analyses confirmed that the gene is expressed in both tissue-derived and laboratory-grown forms of complement-resistant E. histolytica.