The relationship between the variability (relative standard deviation, σ) in mixing ratio of a gas and its global mean lifetime (τ) has been used to estimate the τ of atmospheric gases. This can prove quite useful if it is a unique relationship. Here a three-dimensional chemical transport model is used to investigate the variability-lifetime relationship of tropospheric gases with two types of sources and three types of losses. The effects of sampling time and location are also explored. The relationship is best described in the form σ = ατ−β, where α and β are variable depending on the sources, sinks, and time and location of averaging. When spatially averaging over the troposphere and temporally averaging over 1 year, the model results give a β of 0.77–0.79 for τ between 0.9 and 7.0 years. The variability of a CH3Br-like gas is also analyzed using different weightings of chemical sinks. Photochemical (OH), ocean mixed layer, and soil losses are scaled separately to maintain τ ≈ 1 year. These different scalings result in a ±17% spread in σ, which translates into a ±20% spread in τ inferred from the variability-lifetime relationship found in the model. In addition, the model is used to simulate conditions of Pacific Exploratory Mission (PEM) Tropics A and B field campaigns. The variability-lifetime relationships derived from the model do not compare to the field observations, except that both demonstrate a seasonal dependence of variability. This study identifies some factors controlling the variability of trace gases in the troposphere, estimates the error in using variability-lifetime analysis to determine an unknown τ, and shows that the variability-lifetime relation is not universal among trace gases.