Although the final cumulative exposure has been used as a exposure variable on the cohort study for the relation between exposure and disease, the bias from the use of fixed exposure can be developed because the exposure amount changes across the time. We developed the program to handle the Cox model with irregularly changing time-dependent exposure variable and covariates, and the validity about the application of time-dependent exposure variable and lagged interval was practically evaluated by analyzing the data collected for typical retrospective cohort study with that program. The results were as follows : The exposure-response relations between the deaths from lung cancer and exposures (fixed or time-dependent) were not clear when 0 year lagged interval was applied. When 15 years lagged interval was applied, the exposure-response relations between the deaths from lung cancer and the time-dependent exposures to crystalline silica were observed and relative risky increased like 1.00, 1.17, 1.30 and 2.45 across the exposure levels. The relative risk estimates for lung cancer with time-dependent exposure variable were higher than those with fixed exposure variable without regard to the application of lagged interval. The exposure-response relations between the deaths from non-malignant respiratory disease (NMRD) and exposures (fixed or time-dependent) were observed across exposure levels when 0 year lagged interval was applied. When 15 years lagged interval wag applied, the exposure-response relations between the deaths from NMRD and the time-dependent exposures to crystalline silica were observed, but were not with fixed exposure variable. The relative risk estimates for NMRD mortality with time-dependent exposure variable were higher than those with fixed exposure variable, and the application of lagged interval on the evaluation of NMRD mortality was meaningless. The results suggests that the application of time-dependent exposure variable on the study of exposure-effect relation should be considered and the application of lagged interval should be decided according to the time needed from disease detection to death.