In acute appendicitis, although the relationship between the enteric nervous system (ENS) and mast cells (MCs) has been described in a few studies, neither the expression of nerve growth factor (NGF) nor its relation to mast cell density (MCD) and ENS has been delineated yet in this disease. The aim of this study was to immunohistochemically investigate the relationship between MCD, nervous system and NGF expression in the appendices of cases with clinically and histopathologically diagnosed acute appendicitis and of normal controls. Twenty-five patients with acute appendicitis and twelve normal controls were included in our study. Mast cell tryptase, PGP 9.5 and anti-NGF immunostained tissue sections were subjected to quantitative image analysis. Our results showed that MCD, the number of Schwann cells, the number and size of ganglia and NGF staining were significantly greater in acute appendicitis than in the control group (p < 0.01). A strong correlation between MCD and NGF staining was detected (r = 0.92) only in cases with acute appendicitis. Similarly MCD was also related to neuronal proliferation and hypertrophy in this group. We failed to detect any relationship between NGF staining and neural components either in the acute appendicitis or control groups. Our findings indicate that mast cells could be one of the important cell populations responsible for nerve proliferation and hypertrophy in acute appendicitis. The relationship between NGF staining and MCD and the lack of correlation between NGF staining and changes in neural components suggest that, in acute appendicitis, NGF might be responsible for the increased number of MCs, but not for neuronal proliferation and hypertrophy.