The purpose of this study was to compare substance P (SP) and calcitonin gene-related peptide (CGRP) expression in pulp tissue with clinically diagnosed symptomatic and asymptomatic irreversible pulpitis. Healthy pulps acted as controls. Five normal pulps and 40 with irreversible pulpitis (20 symptomatic and 20 asymptomatic) were obtained from 45 different patients. SP and CGRP expression was determined by competition binding assays using enzyme immunoassay. anova and Mann-Whitney tests were used to ascertain if there were statistically significant differences between the groups. The results showed that neuropeptides were found in all pulp samples. The highest and the lowest expressions for SP and CGRP were found in symptomatic irreversible pulpitis and healthy pulps groups, respectively. The differences between healthy pulps and the groups of pulps having irreversible pulpitis were significant (P < 0.001). Although Mann-Whitney's post-hoc tests showed statistically significant differences in CGRP expression between two pulpitis groups (P < 0.05), differences in SP expression between symptomatic and asymptomatic irreversible pulpitis groups were not significant. This study demonstrated that the expression of CGRP and SP is significantly higher in pulps with irreversible pulpitis compared with healthy pulps.