The popular screen team of Jack Mulhall and Dorothy Mackaill were back again in Smile, Brother, Smile. The stars are cast respectively as hot-shot salesman Jack Lowery and sagacious secretary Mildred Marvin, employees both of a big-time cosmetics company. Inexplicably, the company's sales are dropping, and it looks as though there's going to be some "downsizing" in the near future. Putting their heads together, Jack and Mildred discover that the firm's duplicitous manager Harvey Renrod (Philo McCullough) is actually in the employ of a rival firm. In a fit of euphoria, Mildred sample's some of her company's product and transforms from an ugly duckling into a swan, thereby cinching a fat new contract for her boss and simultaneously winning the love of Jack.