The reversible denaturation and reduction with dithionite has been studied for the phycobiliproteins, C-phycocyanin (1) and allophycocyanin (2) from Spirulina platensis, and C-phycoerythrin (4) from Fremyella diplosiphon (both cyanobacteria). By treatment with sodium dithionite, the chromophores are selectively reduced at the central (C-10) methine bridge, producing pigments with bilirubinoid (lambda max = 418 nm from 1 and 2), and vinylpyrroloc (lambda max= 300 nm from 4) chromophores. The extent of reduction is dependent on the state of the protein. The chromophores of denatured biliproteins are completely reduced at 0.5 mM dithionite. In the native pigments, dithionite concentrations up to 0.5 mM lead only to partial reduction, thus forming products containing both reduced and oxidized chromophores (e.g. "phycocyanorubins" from 1 and 2). The reduction is non-statistical with respect to the different chromophores present in 1 and 4, the chromophores absorbing at shorter wavelengths being preferentially reduced. Renaturation of the proteins containing reduced chromophores is accompanied by their reoxidation. This oxidation is complete in the absence of dithionite or at concentrations up to 0.5 mM. At higher dithionite concentrations, the reoxidation is incomplete, and the products are spectroscopically identical to those obtained by reduction of the native pigments at similar concentrations of reductant. The results are interpreted by a model in which the protein is "transparent" to the reducing agent, dithionite. The difference in the extent of reduction of the native and denatured pigments can only be due to thermodynamic (viz. stability) differences in the susceptibility of the chromophores to reduction. Specifically, the (extended) chromophore present in the native pigment is much more difficult to reduce than the chromophore (present in a cyclic conformation) in the denatured pigment. The energetics of the process of refolding both the protein and the chromophores are discussed.