The International Agency for Research on Cancer has classified nickel compounds as carcinogenic to humans, but it is still not known with certainty which forms of nickel pose the risk. In a case-control study of Norwegian nickel-refinery workers, the authors examined dose-related associations between lung cancer and cumulative exposure to four forms of nickel: water-soluble, sulfidic, oxidic, and metallic. A job-exposure matrix was based on personal measurements of total nickel in air and quantification of the four forms of nickel in dusts and aerosols. Data on smoking habits were collected for 213 cases identified in the Cancer Registry of Norway between 1952 and 1995 and 525 age-matched controls (94% participation rate). The nickel exposures were moderately to highly correlated. A clear dose-related effect was seen for water-soluble nickel (odds ratio = 1.7 per unit in the log(e)-transformed exposure, ln[(cumulative exposure) + 1], originally given in (mg/m(3)) x years (95% confidence interval: 1.3, 2.2)). A general rise in risk from other types of nickel could not be excluded, but no further dose-dependent increase was seen. Smoking was a weak to moderate confounder. The study suggests an important role of water-soluble nickel species in nickel-related cancer.