Following a single oral dose of 1.25 g sulfapyridine (SP), the pharmacokinetic properties of this moiety of sulfasalazine were evaluated in healthy volunteers. While there was no difference in the absorption characteristics, plasma protein binding (49.6 ± 3.3%), and apparent distribution volume (0.9 ± 0.4 liters/kg) between fast (n = 4) and slow (n = 5) acetylators, elimination half-life (5.5 ± 1.2 vs 15.3 ± 2.2 hr: p < 0.0001), and total plasma clearance (135.3 ± 50.3 vs. 36.9 ± 12.2 ml/min: p = 0.002) demonstrated marked differences between these two phenotypes. In 57 patients with Crohn's disease and 47 patients with ulcerative colitis (53% slow and 47% fast acetylators), plasma levels were monitored routinely. Plasma levels were in the suggested “therapeutic” range of 20–50 μg total SP/ml in 60% of patients, which was associated in 53% of the cases with a good therapeutic response. Of the 40% of patients exhibiting plasma levels below 20 μg/ml, only 27% demonstrated a good response. This difference is probably due to the better absorption seen in well-controlled patients. Multiple plasma level determinations over 0.5–2 years were performed in 9 patients with Morbus Crohn and 2 patients with ulcerative colitis. No significant correlation between dose and plasma levels of SP or its acetylated metabolite was found. In addition, neither SP nor total SP plasma levels demonstrated a relationship with the therapeutic response to sulfasalazine. Thus the existence of a so-called “therapeutic” range appears to be highly questionable. Side effects (nausea, headache, vomiting, allergic reactions) were seen with an overall frequency of 17%. In some cases they were associated with high plasma levels.