A carefully chosen selection of CMC polymers was used to probe the depression of talc and chalcopyrite and to highlight the effect of specific alterations of the bulk polymer chemistry on the power and selectivity of the depressants. In situ tapping mode atomic force microscopy (AFM), captive bubble contact angle measurements, and flotation tests were used to study the adsorption of the CMC polymers on chalcopyrite and talc. The degree of substitution and distribution of substitution of carboxymethyl groups on CMC was seen to have a strong influence on the ability of the polymers to adsorb onto the surface of talc and chalcopyrite. High substitution results in low coverage on both minerals whereas low substitution results in higher coverage. The influence of distribution of substitution (random or clustered) was also seen to affect the adsorption, with more random/even substitution giving rise to greater adsorption on talc and chalcopyrite. The contact angle of talc and chalcopyrite is significantly altered in the presence of the three polymers, with increased surface coverage (determined by AFM) correlating with the ability of the polymers to decrease the wettability of talc and chalcopyrite. This trend was also followed in single and mixed mineral talc and chalcopyrite flotation. (C) 2010 Elsevier Ltd. All rights reserved.