Sulfasalazine appears to exert its beneficial effect in colitis by releasing 5-aminosalicylic acid in the colon, but its use can be limited by side effects. Ipsalazide and balsalazide are novel sulfasalazine analogs designed to release 5-aminosalicylic acid and a nontoxic carrier molecule in the gastrointestinal tract. They have a low oral toxicity following single or repeat administration to mouse, rat, and ferret, and balsalazide is not mutagenic in the Ames test. Ipsalazide and balsalazide are split in rat and man, and the urinary and fecal excretion pattern of the 5-aminosalicylic acid released is similar to that of sulfasalazine; the carrier molecules are absorbed to a lesser extent than the sulfapyridine derived from sulfasalazine. These two analogs deserve therapeutic trial.