Nickel (Ni) is the most common contact allergen among the general population in the industrialized world. Ni has been shown to exhibit immunomodulatory, if not immunotoxic, effects in several experiments conducted on humans and on rodents. This study tests the incidence of different infectious diseases in 100 patients with Ni hypersensitivity and compares it to data from 100 healthy volunteers. One hundred subjects with Ni hypersensitivity were enrolled. A group of 100 matched healthy volunteers with negative European standard patch test were enrolled as healthy controls. In patients with Ni hypersensitivity a higher incidence of recurrent herpes labialis (RHL), urinary tract infections (RUTI), genital candidiasis, and upper respiratory tract infections (RURTI) was detected. Fifteen patients with nickel allergic hypersensitivity (NAH) followed a Ni-poor diet. After a one-year diet a net reduction of incidence of RHL was found. Indeed, the number of episodes of RHL per year decreased from 6 +/- 2.75 to 2.4 +/- 1.2. Conversely, among the matched control group with NAH following a normal daily dietary nickel intake the RHL number did not show any statistically significant changes (6.1 +/- 1.7 vs 6 +/- 1.5 ). In conclusion, our study demonstrates a higher incidence of recurrent infections among patients with NAH. A low-Ni diet reduces the number of RHL episodes per year.