Functional expression of gap junction proteins can be obtained conveniently with the paired oocyte cell--cell channel assay. So far all gap junction proteins (connexins), with the exception of one, have been found to make functional channels either by themselves or as hybrid channels (two hemichannels of different connexin composition). Connexin33 (cx33) appears not to follow this rule. Expression of cx33 in oocytes does not yield functional channels, and attempts to identify another connexin with which cx33 can form hybrid channels have failed so far. The observation was made that cx33 inhibits functional expression of other connexins in a connexin-specific way. While expression of cx32 remains unaffected by coinjection into oocytes of cx33 mRNA together with cx32 mRNA, junctional conductance obtained with cx43 is marginally reduced whereas coinjection of cx33 mRNA at equimolar concentrations almost completely abolishes functional cx37 expression. The fact that testis is the only tissue found to express significant levels of cx33 mRNA together with cx37 and cx43 suggests a possible functional role for an inhibitory connexin. A model is proposed where cx33 limits a cell's capability to make functional channels by allowing formation of heterotypic channels with other cells while formation of homotypic channels is disallowed. Such a mechanism would permit asynchronous maturation of germ cells while at the same time allowing communication between germ cells and Sertoli cells.