Summary1. A novel experimental method was developed to study negative physical and chemical effects of latex and cardiac glycosides on first‐instar monarch butterfly larvae in their natural environment in north central Florida. Forceps were used to nibble through the petioles of leaves of the sandhill milkweed Asclepias humistrata, mimicking the behaviour of mature monarch larvae. This notching cut off the supply of latex to the leaves without significantly reducing either their cardiac glycoside concentration or water content.2. The mean cardiac glycoside concentration in larvae that fed on intact leaves was nearly two and a half times greater than in larvae that fed on notched leaves. This was probably because more latex is present in the gut of the larvae that fed on the intact leaves. Supporting this is the fact that the mean concentration of cardiac glycosides in the latex was 34–47 times that in the leaves.3. Wet weights, dry weights, and growth rates of first‐instar larvae that fed on intact leaves over a 72‐h period were less than half those of larvae that fed on notched leaves.4. Mortality due to miring in the latex was 27% on the intact leaves compared with 2% on the notched leaves.5. Latex, cardiac glycosides, and other as yet undetermined plant factors all have a negative effect on first‐instar larval survival.6. Video‐analyses indicated that ingestion of latex caused the larvae to become cataleptic and increased their chances of being mired on the leaf by the setting latex glue. Dysfunction resulting from latex ingestion may lead to the larvae falling off the plant and being killed by invertebrate predators.7. The difficulty of neonate monarch larvae surviving on A. humistrata – one of the principal milkweed species fed on each spring as monarchs remigrate from Mexico into the southern U.S.A. – is evidence that a co‐evolutionary arms race is operating in this plant–herbivore system.