Detrimental elements such as arsenic and antimony tend to accumulate in dusts and drosses of lead-zinc as well as copper smelters. These by-products are commonly treated in dedicated reductive smelting units producing Cu-rich matte, As-Sb-collecting speiss and Pb-rich metal, as well as liquid slag. Such process would have a complex distribution of elements (Cu, Fe, Pb, Zn, Ni, Sn, Sb, As, Ag, Au, S, etc.) among four liquid phases. Thermodynamic calculations can be used for predictions and optimization of such processes. They must rely on accurate models developed in integration with experimental program. Present study reports results of recent progress in experimental and modelling studies of As, Sb-containing speiss systems and demonstration of calculations relevant for industrial conditions. Experimental methodology consisted of equilibration, quenching and electron probe X-ray microanalysis. Calculations were performed using FactSage software and thermodynamic database developed based on the dedicated recent experiments. The main findings of the paper are: a set of binary and ternary diagrams relevant to matte and speiss formation conditions; distribution of Ag and Au among liquid Pb and speiss in key quaternary systems; and distributions of 10 main elements for industrially relevant matte/speiss/metal multicomponent equilibria.