From 1996 to 2001 a total of 467 Staphylococcus hyicus isolates from exudative epidermitis (EE) in pigs in Denmark were examined for susceptibility to 13 different antimicrobial agents. The presence of selected genes encoding macrolide (erm(A), erm(B) and erm(C)), penicillin (blaZ), streptogramin (vat, vga, vga(B), vat(B), vat(D) and vat(E)), streptomycin (aadE) and tetracycline resistance (tet(K), tet(L), tet(M) and tet(O)) were determined in selected isolates. The occurrence of erythromycin resistance increased from 33% in 1996 to a maximum of 62% in 1997 and decreased to 26% in 2001. Resistance to sulphametazole increased from 17% in 1996 to 30% in 1998 but has since decreased to 4% in 2001. Resistance to trimethoprim increased to 51% in 1997 and decreased to 21% in 2001. Resistance to tetracycline (21-31%) remained relatively constant during 1996-2000, but increased to 47% in 2001. Resistance to penicillin (54-75%) streptomycin (33-53%) and tetracycline (21-47%) remained relatively constant over the time investigated. All 48 penicillin resistant isolates examined contained the blaZ gene and 40 (85%) of the streptomycin resistant isolates the aadE gene. It was not possible to detect any streptogramin resistance gene in four streptogramin resistant isolates. Of the 55 erythromycin resistant isolates examined, five contained erm(A), 13 erm(B), 35 erm(C) and two both erm(A) and erm(C). The presence of erm(B) was confirmed by hybridization to plasmid profiles in all 13 PCR-positive isolates. Of 52 tetracycline resistant isolates examined, two contained tet(L), 38 tet(K) and 12 both tet(K) and tet(L).