Polymorphisms in the TAS2R38 gene provide insight to phenotypes long associated 6-n-propylthiouracil (PROP) and phenylthiocarbamide bitterness. We tested relationships between TAS2R38 genotype, taste phenotype, and fungiform papillae (FP) number in 139 females and 59 males (age range 21-60 years), primarily of European ancestry. DNA was analyzed for 3 polymorphic sites, identifying common (alanine-valine-isoleucine [AVI/AVI], heterozygotes, proline-alanine-valine [PAV/PAV]) and rare (proline-valine-isoleucine, alanine-alanine-valine, AAI) forms. Individuals with PROP threshold >0.15 mM were almost exclusively AVI/AVI; those with threshold <0.1 mM could have any genotype. PAV/PAVs were more difficult to identify with PROP taste measures, although perceived bitterness of moderate PROP concentrations (0.32, 1 mM) had better correspondence with genotype than did threshold. For AVI/AVIs, increases in bitterness from 1 to 3.2 mM PROP nearly paralleled those of TAS2R38 heterozygotes and PAV/PAVs. Some bitterness gains were related to FP number sampled from a standard area on the tongue tip, yet the PROP bitterness-FP relationship differed across genotype. Among homozygotes, FP was a significant determinant of PROP bitterness; heterozygotes showed a flat relationship. Those tasting concentrated PROP as more bitter also tasted concentrated sucrose, citric acid, sodium chloride, and quinine as more intense, even after statistically controlling for TAS2R38 genotype, FP, and intensity of tones (nonoral standard). To summarize, although PROP threshold generally exhibited single-gene complete dominance, PROP bitterness may involve additional bitter receptors as evidenced by misclassification of some nontaster homozygotes and the bitterness functions for concentrated PROP. Variability in receptor expression may explain attenuated bitterness-FP relationships. PROP bitterness does associate with heightened taste sensations (i.e., supertasting), but this is not due to TAS2R38 polymorphisms.