Simultaneous intradermal sensitivity testing to Mycobacterium tuberculosis (PPD-S), six different atypical mycobacteria (PPD-A, B, F, G, T, and Y), Coccidioides immitis (coccidioidin), and Histoplasma capsulatum (histoplasmin) was performed on 560 subjects among the relatively isolated island populations of Ifaluk (Caroline Islands), Loh and Merig (New Hebrides), Anuta (Solomon Islands), and in the Mala (Amdei) and Iwane (Simbari) villages of the Anga linguistic groups in the Marawaka area of the Eastern Highlands Province of Papua New Guinea. At the time these tests were performed (Mala and Iwane villages, and Ifaluk Atoll in 1967, and Loh, Merig, and Anuta Islands in 1972), all island populations had already had a long history of sporadic European contact, whereas the New Guinean villages of Mala and Iwane had remained virtually unexposed to the outside world. Using a dose of 0.0001 mg PPD per 0.1 ml (5 TU), and considering induration of at least 10 mm at 48 hours to represent a positive reaction, skin sensitivity to M. tuberculosis was found to be absent among the Anga, and to have an incidence of 11% on Loh, 17% on Merig, 34% on Ifaluk, and 55% on Anuta. Data on the prevalence of tuberculous infection obtained by skin tests reflected the reported prevalence of symptomatic tuberculosis in all groups. The frequency of reactions to 0.0001 mg doses of the atypical mycobacterial antigens corresponded to tuberculin sensitivity in the different groups: none among the Anga, sporadic on Loh and Merig, and common on Ifaluk and Anuta. However, analysis of PPD profiles suggests that atypical mycobacterial infection is probably not occurring in any of these populations. Reactions ≥5 mm to a 0.1 ml dose of 1:100 coccidioidin were observed in 26% of the population of Ifaluk, and of 1:100 histoplasmin in 8% of the population of Anuta, and 14–16% of the populations of the two New Guinean villages.