Much recent work has dealt with water-soluble analogs of the naturally occurring porphyrins as a means of gaining a more detailed understanding of the in viva functioning of such metal macrocyclic complexes [l-9]. Interest in metalloporphyrin-protein complexes arises from the crucial role these species play in a number of biological systems. The role of albumin in heme transport has been recently reviewed [IO] and several studies of the heme-albumin complex have appeared in the literature [l l-15]_ In this communication, we report on the interaction of several water-soluble metalloporphyrins with human serum albumin. We also present new data for the heme-albumin complex which helps to elucidate the difference in interaction between the specific and nonspecific binding sites. Both systems provide complemen+y information which heIps clarify the nature of the protein-porphyrin compbjr. MATERIALS AND METHODS Human serum albumin was obtained from Sigma Chemicals and was defatted according to the method of Chen [16] _ After centrifugation, the supematant was filtered through a 0.22 m Millipore filter and lyophilized. Albumin monomer was obtained by gel-filtration on a column (100 X 2.5 cm) of Sephadex G200 [ 17 ] _ Hemin (recrystallized) was purchased from Nutritional BiochemicaIs Corp. and used without further purification. TMpyP, TCPP, CoTMpyP, CoTCPP and CuTCPPl were prepared as described previously [S, 9, 18, 191. Spectra in