Members of the connexin family differ most in their carboxy-termini, both with respect to sequence and length. In order to assess the contribution of this region to channel function, a series of carboxy-terminal deletion mutants were tested in the paired-oocyte expression system. Connexin-32 can be truncated by 64 amino acids without detectable loss of its known channel properties. Removal of additional amino acids results in a progressive loss of function over a stretch of 4 amino acids. In addition to this effect of length the charge of the carboxy-terminus appears to be another determinant of channel function. One of the fully functional deletion mutants, carrying a stop codon after amino acid-219, had been reported to be associated with Charcot-Marie-Tooth disease. The implications of this finding are discussed.