We report the sequence of a cDNA clone that encodes the C-terminal half of the hamster 94 X 10(3) Mr glucose-regulated protein, grp94. The amino acid sequence of this protein is about 50% homologous to Drosophila hsp83 and yeast hsp90, suggesting that grp94 and hsp90 have similar functional properties. Unlike hsp90, grp94 is associated with the endoplasmic reticulum. It has the same C-terminal tetrapeptide as two other luminal endoplasmic reticulum proteins, grp78 and protein disulphide isomerase. We suggest that this sequence forms part of a signal for retention of proteins in the lumen of the endoplasmic reticulum.