Tuberculin test (purified protein derivative) is currently accepted as a standard investigation used in the diagnosis of tuberculosis (TB). Although the sensitivity of the test is reliable, a substantial number of those subjected to screening for TB by such test are cigarette smokers. This study is designed to investigate the effect of smoking on cell-mediated delayed-type cellular hypersensitivity (DTH) reaction by PPD. Prospective, case-control study was conducted at the Chest and TB unit of Chest Hospital Kuwait. The study population consisted of 357 healthy volunteers serving as controls and 200 in-patients under direct medical supervision and treatment for tuberculosis as cases. The mean age was 33.69 +/- 8.6 SD; 286 were current smokers and 271 were lifetime non-smokers. PPD test was done using 2TU RT23 SSI-Denmark on all subjects. Median PPD was significant among the cases (P=0.03) between smokers and non-smokers and was highly significant among the healthy controls (P<0.001). No significant difference was seen between median pack years of smoking and PPD levels among the patient group (P=0.264) but the difference was significant among the control group (P<0.001). Univariate analysis of variance (ANOVA) on PPD, taking into account age, pack years of smoking, ethnic groups and BCG scar showed sufficient response but was not statistically significant to all these factors. Smoking habit does not appear to influence the cutaneous delayed type hypersensitivity reaction by tuberculin skin test.