One challenge in microarray experiments is assessing when the results are biologically significant. This assessment can be aided by detailed annotation of the probeset target sequences, including gene function or category, protein product, and pathway information. NetAffx compiles public and in-house annotations for all Affymetrix chip sets. Public annotations are collected from Unigene, LocusLink and Swiss-prot. In-house annotations are produced by Generalized Rapid Automated Protein Analysis (GRAPA), a high-accuracy HMM method for protein annotation. GRAPA has been used to generate novel annotations under three classification schemes: Structural Classification of Proteins (SCOP), Enzyme Commission (EC), and G protein coupled receptors (GPCR). In addition, annotations are generated by searching Pfam and BLOCKS databases. These annotation schemes have been applied to diverse genomes including human, mouse, rat, drosophila, and yeast, then mapped onto Affymetrix microarray probesets. The combination of protein-level annotations with public source annotations creates a powerful description of genes at both the genomic and protein levels. Users can collect information on a target sequence, or cluster microarray probe sets according to a given domain or functional category. NetAffx is available on the web at http://www.NetAffx.com/.