This study presents a comparative drug–protein, in vitro, binding profile of sodium aurothiomalate and auranofin. It was found that about 40% of total protein-bound gold is attached to albumin after incubation of aurothiomalate with whole blood for 24 h and about 29% of it was with α1-globulin and the least amount was found with γ-globulin (6.1%). On the other hand, approximately 84% of the protein-bound auranofin gold attached to globulins of which 51% was found with β-globulin band. It was almost equally distributed among albumin, α2-globulin and γ-globulin, and showed least affinity for α1-globulin. The gold analyses were performed by standardless instrumental neutron activation method duly validated by use of an established atomic absorption method. The results of this study explain to some extent the difference in, in vivo, pharmacokinetics and pharmacodynamics of the two drugs.