The chemical activity of organic chemicals directs their diffusion and partitioning and is consequently crucial for their transport, distribution, and toxic effects. A silicone membrane equilibrator is introduced for measuring the chemical activity of nonpolar organic chemicals in lipidrich samples: (1) A 6 m poly(dimethylsiloxane) (PDMS) microtube (300 mu m i.d., 640 mu m o.d.) was placed in a sample, and a sample-PDMS equilibrium was reached within 10 min for 12 polycyclic aromatic hydrocarbons (PAHs) acting as model compounds. (II) A plug of 100 mu L of methanol was pushed through the tube to equilibrate it with the PDMS and thus the sample. (III) This yielded an undiluted methanol extract that was injected into a high-performance liquid chromatograph (HPLC) with multiband fluorescence detection. Quantification limits expressed as unitless chemical activities ranged from 6 x 10(-9) to 5 x 10(-8), and relative standard deviations were from 6% to 19%. Chemical activities of PAHs in mussels from two polluted sites were measured between 10(-7) and 10(-5), and activity coefficients for PAHs in vegetable and fish oils hardly differed between oils. This method can be used for internal exposure measurements, for monitoring product safety/conformity, and process control. The method can also be applied to measure total analyte concentrations in lipid-rich samples and oils.