Coloring agents are frequently added to drugs, foods, and cosmetics. If approved by the FDA, these additives may be added or substituted without notifying physicians. A patient developed angioedema, wheezing, urticaria, and dizziness one hour after taking the first Premarin tablet from a new refill. She had previously tolerated Premarin daily for 7 months without any adverse reactions. The new tablets were noted to be a slightly different shade of maroon and subsequent investigation revealed that the dye formulation had been changed (FD&C red #3 and FD&C yellow #6 were changed to FD&C red #40 and D&C #27). Puncture skin testing with a suspended tablet from the new Premarin batch was positive but was negative to a different drug (dye-free). Premarin skin testing in two normal volunteers was negative. The patient has since tolerated transdermal estrogen without any adverse reactions. These findings suggest that an additive in the Premarin tablet, most likely one of the new dyes, and not the estrogen, was the cause of the anaphylaxis. Physicians need to be aware that inactive ingredients can be changed without warning and these new constituents may cause sudden and potentially very severe allergic reactions to previously tolerated medication.