Transcripts of the human IFN alpha-receptor (IFNAR) gene, lacking the transmembrane (TM) domain were found in human myeloma U266S cells, in addition to the transmembranal IFNAR cDNA. Two different cDNAs encoding such soluble IFNAR forms were identified. Form 1 has a deletion causing a frameshift toward the end of the extracellular (EC) domain predicting a tail of 7 amino acids. Form 2 has two in-frame deletions and conserves most of the intracytoplasmatic domain of IFNAR. The transcripts for the two soluble forms are still found in U266R cells which have lost the transmembranal IFNAR transcript. Human cells seem to have independent mechanisms to synthesize soluble IFN receptors, which may act as competitors outside the cells or carry IFN-mediated functions inside the cell.