We studied plasma calcitonin gene-related peptide (CGRP) levels in obese women before (n = 24) and after (n = 13) weight loss, and in normal weight controls (n = 15). Furthermore, the influence of two isocaloric meals (high carbohydrate vs. high fat) on plasma CGRP concentrations was studied. The CGRP concentration in the obese group (32.26 +/- 2.01 pg/ml) was significantly (p less than 0.0001) higher than in the control group (21.64 +/- 0.15 pg/ml). After weight loss (14.3 +/- 0.72% of original weight) CGRP concentrations remained unchanged. Only the high-fat meal caused a significant (p less than 0.02) rise in CGRP levels. Our results indicate that elevated plasma CGRP levels may constitute a primary phenomenon in obese women, and that fat intake may be associated with increased CGRP secretion.