Immunologically reactive protein substances were extracted from bone samples of an American mastodon (Mammut americanum), 10,200 yr old by radiocarbon dating, and from muscle samples of three woolly mammoths (Mammuthus primigenius), 10,000, 40,000 and 53,000 yr old, respectively. The mastodon samples contained significant quantities of the amino acids hydroxylysine and hydroxyproline, both of which are usually found in collagens and not in albumins. Using these products and other comparable extracts, as well as sera and purified collagens from modern elephants and other living mammals, as test antigens, immunological comparisons were carried out with the following antisera: rabbit anti-mastodon bone; chicken anti-mammoth muscle; chicken anti-elephant muscle; rabbit anti-elephant albumin and rabbit anti-elephant collagen, as well as with rabbit antisera to purified albumins and collagens of other mammals. For the first time, mastodon bone was found to have elephant-like proteins, which elicited antibodies that reacted strongly with collagen and serum proteins of extant elephants. Mammoth muscle strongly reacted with anti-elephant collagen and anti-elephant albumin, but the concentrations of the recoverable mammoth collagen and albumin decreased with increasing chronological age of the mammoth specimens. Nevertheless, in the immunological comparisons, the mammoth was closer to Asian (Elephas maximus) and African (Loxodonta africana) elephants than to the mastodon; in turn, the mastodon was closer to these elephantid species than to mammals outside the order Proboscidea.