Because of anthropogenic increases in atmospheric CO₂ content, there is a need to understand how organisms sense and respond to CO₂ variation. An important distinction is whether CO₂ responses result from direct effects of CO₂ on signal-transduction pathways, enzyme catalysis, or regulatory processes, as opposed to indirect, secondary responses that are a consequence of the direct effects. In plants, direct effects occur because rising CO₂ A) increases the activity of Ribulose-1,5-bisphopshate carboxylase/oxygenase (Rubisco) via its role as a substrate for RuBP carboxylation and its inhibition of RuBP oxygenation; B) reduces stomatal aperture; C) alters mitochondrial respiration; and D) possibly reduces transcription of genes for Rubisco activase and carbonic anhydrase. Because of these direct effects, the carbon and water balance of plants is altered leading to secondary effects on growth, resource partitioning and defense compound synthesis. Reduced investment in photosynthetic protein is one of the characteristic acclimation responses of plants to high CO₂. This is modulated by increased carbohydrate levels, probably in concert with hormone signals from the roots. Roots are hypothesized to be the main control points for CO₂ acclimation because they are well situated to integrate the carbohydrate status of the plant. In higher fungi, development of the mushroom fruiting body is inhibited at high CO₂, but the mechanism is poorly known. Fungal CO₂ sensing may serve to position the spore-bearing tissue above the soil boundary layer to ensure effective spore dispersal. The animals that are most sensitive to anthropogenic CO₂ enrichment are insects. Many insects have a well-developed ability to sense CO₂ variation as a means of locating food. Unlike plants, insects have CO₂ receptors that can detect variation in CO₂ as low as 0.5 ppm. However, the sensitivity of these receptors is reduced in atmospheres with double or triple current levels of CO₂, indicating some insect species may be threatened by rising atmospheric CO₂.