We investigated expression of a human p53-inducible gene, P2XM, a member of the P2X-receptor family of ATP-gated ion channels, in 56 human primary soft-tissue tumours including 47 sarcomas and nine benign tumors. Among the 47 sarcomas examined by reverse transcription polymerase chain reaction, 12 had lost expression of this gene and 22 revealed altered splicing patterns; among the nine benign tumours, four showed no expression of P2XM and three revealed aberrant splicing patterns involving transmembrane domains M1 and/or M2. As the aberrant transcripts lacked either or both of those domains, the protein products probably lacked normal function. We also looked for p53 mutations and mdm2 overexpression in the same panel of tumours and found them in 13 tumours, all but three of which had shown altered expression of P2XM. However, 31 (72%) of the 43 tumours that carried wild-type p53 without mdm2 overexpression had revealed aberrant P2XM expression. Our results suggest that disorder of P2XM expression may play a crucial role in the genesis of benign and malignant tumours in soft tissues, and that one or more genetic factors other than p53 or mdm2 contribute significantly to aberrant P2XM expression.