The world's oceans are iron-deficient environments and there is little knowledge available regarding iron uptake by marine sponges. To understand iron-related biofunctions in marine organisms, iron-binding natural compounds from marine sponges were investigated. Here we reported a natural compound haliclonamide A and its analogue haliclonamide B were isolated from the marine sponge Haliclona sp. and their structures were investigated by spectroscopic analysis. The structure of haliclonamide A was determined to consist of novel cyclic peptides containing oxazole and methyloxazoline rings. Mass spectra revealed that these two compounds formed a 1:1 stable complex with trivalent iron but not with divalent iron. EPR analysis showed that these compounds will bind with Fe(III) and Cr(III) specifically, but will not bind to other cation ions such as CU2+, Zn2+, CO2+, Ni2+, Al3+, and Ti3+. The binding constant of compound-iron complex was 10(19) which is lower than the binding constant of siderophores. The Fe(III) concentration in this sponge tissue was shown to be 10 and 100 times higher than the other sponge tissues and seawater. This indicated the sponge Haliclona sp. may possibly uptake iron through nonsiderophore metal-binding peptides haliclonamides A and B. It also suggests that iron uptake activity of marine organisms may occur through nonsiderophore metal-binding peptides in natural ocean.