The catabolism of insulins modified at the A1, B1 or B29 positions or containing a synthetic crosslink between the A1 and B29 positions has been studied in vivo and in vitro. The metabolic clearance rates (MCR) of insulin, proinsulin and chemically modified insulins have been measured by a priming-dose constant infusion technique in greyhounds. Insulins modified at A1 and B29, particularly the crosslinked materials, had markedly lowered MCR's whilst B1 analogues did not differ from insulin. Proinsulin and the A1-B29 crosslinked materials showed a markedly lowered degradability by glutathione-insulin transhydrogenase.