AbstractThe human complement factor H is an important component in the control of the alternative pathway of complement activation. We have previously shown that at least three factor H homologous mRNA species of 4.3 kb, 1.8 kb and 1.4 kb in length are constitutively expressed in human liver. In addition, several factor H‐related proteins have been detected in human sera using antibodies directed against the classical human factor H glycoprotein of 150 kDa. The structure of the additional polypeptides has not been shown so far. Circumstantial evidence suggests that the 1.8‐kb mRNA might encode the 43‐kDa factor H‐like polypeptide. Here we report the isolation, characterization and eukaryotic expression of the first full‐length cDNA representing the major 4.3‐kb mRNA and the 1.8‐kb mRNA of human factor H. We show that the 4.3‐kb transcript encodes the 150‐kDa‐factor H glycoprotein and the 1.8‐kb mRNA the 43‐kDa factor H polypeptide. The identity of the two cDNA in a region of 1400 nucleotides suggests that the two factor H‐related transcripts are derived from one gene by a process of alternative splicing.