Although it is beyond doubt that mammary cells accumulate iodide via a Na+-dependent transport mechanism, it is not clear if this is the only pathway for iodide transport in mammary tissue. In view of this, experiments were designed to test for the presence of an anion-exchange pathway which could mediate the transport of iodide into mammary cells; thus, the effect of external iodide on sulfate efflux from rat mammary tissue has keen investigated. Iodide trans-stimulated sulfate efflux from mammary tissue explants in a dose-dependent manner: 0.1, 1.0 and 10.0 mM iodide stimulated the fractional release of iodide by 56 +/-2,2, 166.5 +/- 17.5, and 302.9 +/- 29.8%, respectively. The stimulation of sulfate efflux by external iodide was completely inhibited by DIDS (4.4'-diisothiocyanatostilbene 2,2'-disulfonic acid). Perchlorate (1 mM) also trans-stimulated sulfate efflux in a manner that was inhibited by DIDS, Furthermore, iodide trans-accelerated sulfate efflux from rat mammary acini via a DIDS-sensitive mechanism. The results are consistent with the presence of a DIDS-sensitive anion-exchange mechanism which can accept iodide as a substrate. It appears that the iodide-sulfate exchange mechanism is independent from the sodium-dependent iodide transporter given that sulfate is not a substrate of the latter system. The iodide-sulfate exchanger may operate in parallel with the sodium-dependent iodide transporter to mediate iodide uptake into mammary cells.