Aim: To assess immunohistochemical evaluation of neuronal dysfunction in pelviureteric junction obstruction. Material And Methods: Present study was conducted in Department of Pathology in collaboration with Department of Pediatric Surgery, Pt. B D Sharma PGIMS, Rohtak (Haryana). Forty five specimens of resected portion of pelviureteric junction during pyeloplasty from cases of primary pelviureteric junction obstruction constituted the study group. Patients with pelviureteric junction obstruction other than primary obstruction such as obstruction secondary to stones, external pressure, previous surgery etc. were excluded. Eleven specimens of normal PUJ obtained at autopsy of age matched pediatric population constituted the control group. The specimens were fixed and examined grossly for any macroscopic abnormality. Specimens were processed from pelviureteric junction and upper and lower resected margins. An attempt was also made to process the whole specimen and sections included both the cut ends. Sections were processed by routine histological technique for paraffin embedding. Results: Significant transmural inflammation was seen in 2 cases while 2 other cases showed lymphoid follicles formation in the wall. Lamina propria showed significant fibrosis in 7 cases (15.6%) and was seen only in cases of PUJ obstruction so it was a highly significant finding (p < 0.001). The difference of mean positivity was highly significant (p value=0.0001) and presence of 3 or less ICC was significantly associated with PUJ obstruction (38 of 45 cases). Although not significant statistically (p value = 0.172), the mean number of Synaptophysin positive cells was less in PUJ obstruction cases (3.84±3.4/HPF) than controls (6.36±5.36/HPF). Conclusion: Neuronal markers showed consistent decreased expression of CD117 with a tendency for other neuronal markers (S-100 and Synaptophysin) to be expressed at level lower than normal indicating thereby neuronal dysfunction with reduced neuronal drive as primary defect in PUJ obstruction and the muscular changes being secondary as a compensatory mechanism.