Secretogranin II (SgII) is an acidic secretory protein present in large dense core vesicles of neuronal and endocrine cells. Based on the sequence of a peptide derived from the processing of SgII in the brain of the frog Rana ridibunda, degenerate oligonucleotides were used to clone the cDNA encoding frog SgII from a pituitary cDNA library. This cDNA encodes a 574 amino acid protein which exhibits 46–48% sequence identity with mammalian SgII and contains 11 pairs of basic amino acids. Four potential processing products delimited by pairs of basic residues exhibited a much higher degree of identity (68–82%) with the corresponding mammalian SgII sequences. The frog SgII mRNA is ∼4 kb in length and is differentially expressed in the brain and endocrine tissues. The present data reveal that several SgII-derived peptides have been highly conserved during evolution, suggesting that these peptides may play important neuroendocrine regulatory functions.