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The duration of macrocytosis after stopping zidovudine (ZDV) is unknown. Among 104 HIV-infected patients treated with ZDV for more than 1 year, 84 patients had macrocytosis at ZDV discontinuation. The median mean corpuscular volume (MCV) was 114.6 fL (range 100-128 fL). Patients were divided into 2 groups: those who did (resolved macrocytosis, n = 36) and did not (persistent macrocytosis, n = 48) normalize MCV at 3 to 6 months after ZDV discontinuation. Alcohol use (P =.02), smoking (P =.03), and lower (but within normal range) folic acid levels (P =.05) were related to the persistence of macrocytosis. A persistence of macrocytosis was observed in 57% at 3 to 6 months, 38% at 1 year and 37% at 2 years after ZDV therapy had stopped. Duration of ZDV therapy did not have an effect on the persistence of macrocytosis (P =.73). The median time for the MCV to normalize after stopping ZDV was 12.5 months.