A review. The anal. methodol. for speciation of metals and metalloids assocd. with alkyl groups and biomacromols. is critically reviewed. Alkylated metals and metalloids are not only known to be produced by microbial methylation within most anaerobic compartments in the environment, but also in the course of enzymic transformations during human metab. Because of the toxicol. relevance of these compds. present in trace to ultratrace concns., firm species identification and exact quantification are essential. While many instrumental techniques coupling chromatog. (GC, HPLC, CE, GE) with plasma mass spectrometry (ICP-MS) are available for quantification, methods used for structural identification often suffer from inadequate sensitivity (EI-MS, ESI-MS, MALDI-MS, FT-ICRMS). Other problems encountered are sample derivatization artifacts, lack of suitable stds. for quantification, lack of equil. between spikes and sample, and the integrity of metal-protein assocn. during sepn., in particular during SDS-PAGE. Selected application examples with respect to mercury and arsenic speciation will be discussed critically.