A cDNA coding for a new subunit of soluble guanylyl cyclase with a calculated molecular mass of 81.7 kDa was cloned and sequenced. On the basis of sequence homology, the new subunit appears to be an isoform of the α 1 -subunit and was designated α 2 as the new subunit is very similar to the α 1 -subunit in the middle and C-terminal part: it is quite diverse in the N-terminal part. Preceding experiments had shown that coexpression of the α 1 - and β 1 -subunits is necessary to obtain a catalytically active guanylyl cyclase in COS cells [(1990) FEBS Lett. 272, 221-223]. The finding that the α 2 -subunit was able to replace the α 1 - but not the β 1 -subunit in expression experiments demonstrates the interchangeability of the α-subunit isoforms of soluble guanylyl cyclase.